Parathyroid hormone decreases renal vitamin D receptor expression in vivo

The vitamin D receptor (VDR) is a nuclear transcription factor responsible for mediating the biological activities of 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. Renal and parathyroid gland VDR content is an important factor in calcium homeostasis, vitamin D metabolism, and the treatment of secondary hyperparathyroidism and renal osteodystrophy. In these tissues, VDR expression is highly regulated by the calcium and vitamin D status. Although 1,25(OH)(2)D-3 up-regulates VDR expression, hypocalcemia and vitamin D deficiency result in drastically reduced expression of the receptor. The generation of 25-hydroxyvitamin D-3-1 alpha-hydroxylase-null mice, which are incapable of endogenously producing 1,25(OH)(2)D-3, has allowed us to investigate the influence of parathyroid hormone (PTH) on VDR expression independent of PTH-mediated increases in 1,25(OH)(2)D-3. Administration of human PTH (1-34) (110 mu g/kg per day) for 48 h reduced renal VDR levels from 515 to 435 fmol/mg protein (15%, P < 0.03) in wild-type mice. In the 25-hydroxyvitamin D-3-1 alpha-hydroxylase-null mice, PTH administration strongly reduced renal VDR levels, from 555 to 394 fmol/mg protein (29%, P < 0.001). These results demonstrate that PTH is a potent down-regulator of VDR expression in vivo.